This research proposal describes comparative immunologic studies on the multiple paraproteins present in the sera of 3 individual patients. The research plans include studies of the respective idiotypic antigenic determinants of the paraproteins, N-terminal amino acid sequence analyses of the respective VH and VL regions, and where available, immunofluorescent analysis of the responsible lymphocytes and plasma cells obtained from these patients. Three pairs of paraproteins have been under study in this laboratory for the past several years. The constituent proteins are: an IgM lambda and an IgG Kappa from an individual patient Br, and IgM Kappa and an IgG Kappa from patient Ca, and 2 IgG Kappa paraproteins of differing electrophoretic mobilities from patient Th. Thus far, the individual pairs of paraproteins have displayed shared idiotypic antigenic determinants. Moreover, the Ca and Th paraproteins have shown sequence homology within their respective VH and VL regions. The Br proteins have been shown to share a VH idiotypic determinant, however the VH regions of the respective Mu and Gamma heavy chains are of separate VH subclass. Attempts are now in progress to complete the entire VH region sequences of these 2 idiotypically related heavy chains. This research proposal includes plans to further identify the sequence homologies responsible for the shared idiotypic determinants in the 3 pairs of paraproteins. Final genetic interpretation of these results await the completion of these sequences. BIBLIOGRAPHIC REFERENCES: Hopper, J.E., Noyes, C., Heinrikson, R. and Kessel, J.W. 1976. Comparative Studies on Monotypic IgM lambda and IgG kappa from an Individual Patient. II Amino-Terminal Sequence Analyses. J. Immunol. 116, 743. Capra, J.D., and Hopper, J.E., 1976. Comparative Studies on Monotypic IgM lambda and IgG kappa from an Individual Patient. III. The Complete Amino Acid Sequence of the VH Region of the IgM Paraprotein. Immunochem. (in Press).